Living with major depressive disorder (MDD) reduces life expectancy, with respiratory disease being a significant threat. However, evidence on respiratory disease in this population has not yet been meta-analyzed.

This meta-analysis examines respiratory disease prevalence and odds ratio (OR) in patients with MDD and treatment resistant depression (TRD). A systematic literature search was conducted, with a snowball search of reference and citation lists. Inclusion criteria covered studies in MDD and TRD patients with confirmed diagnoses of respiratory diseases (asthma, chronic obstructive pulmonary disease [COPD], pneumonia, lung cancer, and tuberculosis), comparing with a control group when possible.

From 4,138 retrieved articles, 15 (including 476,927 individuals with MDD, 50,680 with TRD, and 1,108,979 control group) met the inclusion criteria. In MDD patients, COPD prevalence was 9.0% (95% CI: 3.8–19.6%), asthma 8.6% (95% CI: 5.7–12.8%), and pneumonia 2.5% (95% CI: 2.2–2.9%). In TRD patients, COPD prevalence was 9.9% (95% CI: 4.2–21.9%) and asthma 10.9% (95% CI: 10.7–11.2%), but meta-analysis limited to those diseases showed no significant relative risk differences. Compared to the general population, individuals with MDD had significantly higher rates of COPD (OR 1.79, 95% CI: 1.49–2.16), even higher in younger populations (1.85 [95% CI: 1.74–1.97]) and more prevalent in women.

This first meta-analysis on this topic shows that MDD is associated with an increased risk of respiratory illness compared to the general population. The prevalence of asthma doubles the mean described in the general population worldwide, and in COPD, women and younger people are at particular risk. Prevention policies are urgently needed.

Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.

We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10–28 years; N = 4,835) and UK Biobank (39–86 years; N = 39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points = 11) and the Patient Health Questionnaire-2 in UK Biobank (max time points = 8).

Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.

These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.

Childhood maltreatment (CM) significantly increases the risk of developing post-traumatic stress disorder (PTSD) for which the prevalence in Europe is higher than initially assumed. While the high economic burden of PTSD is well-documented, little is known about the health care cost differences between individuals with PTSD-CM and those without PTSD in Germany. This study aimed to determine the excess health care and absenteeism costs associated with PTSD-CM in Germany.

Baseline data from a multi-center randomized controlled trial on individuals with PTSD-CM (n = 361) were combined with data from individuals without PTSD (n = 4760). Entropy balancing was used to balance the data sets with regard to sociodemographic characteristics. Six-month excess health care costs from a societal perspective were calculated for 2022, using two-part models with logit specification for the first part and a generalized linear model for the second part.

The total six-month excess costs associated with PTSD-CM were €8864 (95% CI: €6855 to €10,873) per person. Of this, the excess health care costs accounted for €4647 (95% CI €3296 to €5997) and the excess costs of absenteeism for €4217 (95% CI: €3121 to €5314). Individuals with mild to moderate PTSD symptoms incurred total excess costs of €6038 (95% CI: €3879 to €8197), while those with severe to extreme symptoms faced €11,433 (95% CI: €8220 to €14,646).

Excess health care and absenteeism costs associated with PTSD-CM were substantial, with absenteeism accounting for roughly half of the total excess costs.

Treatment-resistant depression (TRD) affects 10–30% of patients with major depressive disorder, leading to increased comorbidities, higher mortality, and significant economic and social burdens. This study aimed to compare the efficacy and safety of bupropion and aripiprazole as augmentation therapies for TRD.

This population-based, retrospective cohort study included adults aged ≥18 years with a diagnosis of depressive disorder who met the criteria for TRD. Data were collected from a nationwide claims database in South Korea. Patients prescribed bupropion were matched 1:1 with those prescribed aripiprazole. Subgroup analyses were performed according to age. An as-treated analysis was performed as the primary analysis, and an intention-to-treat analysis was performed to identify different risk windows. The primary outcome was depression-related hospitalization, and the secondary outcomes were first-time diagnoses of movement disorder and seizure.

A total of 5,619 patients (bupropion: n = 1,568; aripiprazole: n = 4,051) were included in this study. Bupropion was associated with lower risks of hospitalization (hazard ratio [HR]: 0.51; 95% confidence interval [CI] 0.29–0.86) and movement disorders (HR: 0.56; 95% CI 0.36–0.85) than aripiprazole. No significant difference in seizure risk (HR: 0.65; 95% CI 0.30–1.31) was observed between the two treatments. The subgroup analysis of participants aged ≥60 years revealed no significant differences in the three outcomes between the two medications.

Bupropion augmentation is associated with a significantly lower risk of depression-related re-hospitalization and movement disorders in patients with TRD. Therefore, bupropion augmentation can be a comprehensive treatment strategy for TRD.

Transcranial direct current stimulation (tDCS) is a promising treatment for major depressive disorder (MDD). This study evaluated its antidepressant and cognitive effects as a safe, effective, home-based therapy for MDD.

This double-blind, sham-controlled, randomized trial divided participants into low-intensity (1 mA, n = 47), high-intensity (2 mA, n = 49), and sham (n = 45) groups, receiving 42 daily tDCS sessions, including weekends and holidays, targeting the dorsolateral prefrontal cortex for 30 minutes. Assessments were conducted at baseline and weeks 2, 4, and 6. The primary outcome was cognitive improvement assessed by changes in total accuracy on the 2-back test from baseline to week 6. Secondary outcomes included changes in depressive symptoms (HAM-D), anxiety (HAM-A), and quality of life (QLES). Adverse events were monitored. This trial was registered with ClinicalTrials.gov (NCT04709952).

In the tDCS study, of 141 participants (102 [72.3%] women; mean age 35.7 years, standard deviation 12.7), 95 completed the trial. Mean changes in the total accuracy scores from baseline to week 6 were compared across the three groups using an F-test. Linear mixed-effects models examined the interaction of group and time. Results showed no significant differences among groups in cognitive or depressive outcomes at week 6. Active groups experienced more mild adverse events compared to sham but had similar rates of severe adverse events and dropout.

Home-based tDCS for MDD demonstrated no evidence of effectiveness but was safe and well-tolerated. Further research is needed to address the technical limitations, evaluate broader cognitive functions, and extend durations to evaluate its therapeutic potential.

The lifetime prevalence of PTSD ranges from 6 to 20% and is often associated with comorbid disorders. Despite the significant impact of PTSD, specific data on healthcare utilization related to PTSD remain limited. This study aims to characterize PTSD-related hospitalizations in France over the past decade.

This nationwide longitudinal retrospective study analyzed PTSD-related hospitalizations in France from 2013 to 2022 using the French National Hospitals Database. Data included discharge records from general and psychiatric hospitals, detailing demographics, admission/discharge dates, ICD-10 diagnoses, and hospitalization specifics.

Between 2013 and 2022, 69,108 patients underwent 125,349 hospitalizations with a PTSD diagnosis (0.4% of all inpatient cases) in France. Psychiatric facilities accounted for 74,988 hospitalizations (1% of all psychiatric inpatient cases in France), while general hospitals recorded 50,361 hospitalizations (0.02% of all non-psychiatric inpatient cases). The percentage of inpatients diagnosed with PTSD increased from 0.68 to 2.22% in psychiatric facilities and from 0.02 to 0.04% in general hospitals over the study period. Females were younger in both settings and had longer stays compared to males in psychiatric facilities. Over time, there was a decrease in median age and an increase in part-time hospitalizations in psychiatric facilities. Mood disorders, stress-related disorders, and substance use disorders were prevalent comorbidities in both settings.

This study highlights a rise in PTSD-related hospitalizations in France, particularly in psychiatric facilities and after 2019, with high rates among women and an increase in hospitalization of younger individuals. These findings highlight the necessity for improved care strategies tailored to the increasing number of younger patients with PTSD.

This systematic review and meta-analysis evaluates the prevalence of disruptive mood dysregulation disorders (DMDD) in community-based and clinical populations.

PubMed and PsychINFO databases were searched, using terms specific to DMDD, for studies of prevalence and comorbidity rates conducted in youths below 18.

Fourteen studies reporting data from 2013 to 2023 were included. The prevalence of DMDD in the community-based samples was 3.3% (95% confidence interval [CI], 1.4–6.0) and 21.9% (95% CI, 15.5–29.0) in the clinical population. The differences in the identification strategy of DMDD were associated with significant heterogeneity between studies in the community-based samples, with a prevalence of 0.82% (95% CI, 0.11–2.13) when all diagnosis criteria were considered. Anxiety, depressive disorders, and ADHD were the most frequent comorbidity present with DMDD. The association with other neurodevelopmental disorders remained poorly investigated.

Caution is required when interpreting these findings, considering the quality of the reviewed data and the level of unexplained heterogeneity among studies. This review stresses the importance of considering a strict adhesion to DMDD criteria when exploring its clinical correlates.

Estimating the risk of developing bipolar disorder (BD) in children and adolescents (C&A) with depressive disorders is important to optimize prevention and early intervention efforts. We aimed to quantitatively examine the risk of developing BD from depressive disorders and identify factors which moderate this development.

In this systematic review and meta-analysis (PROSPERO:CRD42023431301), PubMed and Web-of-Science databases were searched for longitudinal studies reporting the percentage of C&A with ICD/DSM-defined depressive disorders who developed BD during follow-up. Data extraction, random-effects meta-analysis, between-study heterogeneity analysis, quality assessment, sub-group analyses, and meta-regressions were conducted.

Thirty-nine studies were included, including 72,371 individuals (mean age=13.9 years, 57.1% females); 14.7% of C&A with a depressive disorder developed BD after 20.4–288 months: 9.5% developed BD-I (95% CI=4.7 to 18.1); 7.7% developed BD-II (95% CI=3.2% to 17.3%); 19.8% (95% CI=9.9% to 35.6%) of C&A admitted into the hospital with a depressive disorder developed BD. Studies using the DSM (21.6%, 95% CI=20.2% to 23.1%) and studies evaluating C&A with a major depressive disorder only (19.8%, 95% CI=16.8% to 23.1%) found higher rates of development of BD. Younger age at baseline, a history of hospitalization and recruitment from specialized clinics were associated with an increased risk of developing BD at follow-up. Quality of included studies was good in 76.9% of studies.

There is a substantial risk of developing BD in C&A with depressive disorders. This is particularly the case for C&A with MDD, DSM-diagnosed depressive disorders, and C&A admitted into the hospital. Research exploring additional predictors and preventive interventions is crucial.

Quality of life is decreased in bipolar disorders (BD) and contributes to poor prognosis. However, little is known about the causal pathways that may affect it. This study aimed to explore health-related QoL (HRQoL) in BD and investigate its relationship with cognition and psychosocial functioning.

This multicenter cross-sectional study used a neuropsychological battery to assess five cognition domains. Functioning was evaluated using global and domain-based tools, and health-related HRQoL was assessed using the EQ-5D-3L. Structural equation modeling was used to test whether the association between cognition and HRQoL would be mediated by functioning in BD while controlling for covariates such as residual depression, anxiety, antipsychotic medication, and psychotic features.

We included 1 190 adults with euthymic BD. The model provided a good fit for the data. In this model, the direct effect of cognition on HRQoL was not significant (β = − 0.03, z = −0.78, p = 0.433). The total effect of cognition on HRQoL was weak, albeit significant (β = 0.05, z = 3.6, p < 0.001), thus suggesting that cognition affected HRQoL only indirectly through functioning. Anxiety was associated with decreased functioning (β = −0.27, z = −7.4, p < 0.001) and QoL (β = −0.39, z = −11.8, p < 0.001).

These findings suggest that improving cognition may not directly lead to a higher HRQoL. Cognitive remediation is expected to improve HRQoL only through functioning enhancement. They also reveal the potential importance of functional remediation and reduction of comorbid anxiety symptoms in improving HRQoL in BD.

Stressors across the lifespan are associated with the onset of major depressive disorder (MDD) and increased severity of depressive symptoms. However, it is unclear how lifetime stressors are related to specific MDD subtypes. The present study aims to examine the relationships between MDD subtypes and stressors experienced across the lifespan while considering potential confounders.

Data analyzed were from the Zone d’Épidémiologie Psychiatrique du Sud-Ouest de Montréal (N = 1351). Lifetime stressors included childhood maltreatment, child–parent bonding, and stressful life events. Person-centered analyses were used to identify the clusters/profiles of the studied variables and multinomial logistic regression analyses were performed to examine the relationships between stressors and identified MDD subtypes. Intersectional analysis was applied to further examine how distal stressors interact with proximal stressors to impact the development of MDD subtypes.

There was a significant association between proximal stressors and melancholic depression, whereas severe atypical depression and moderate depression were only associated with some domains of stressful life events. Additionally, those with severe atypical depression and melancholic depression were more likely to be exposed to distal stressors such as childhood maltreatment. The combinations of distal and proximal stressors predicted a greater risk of all MDD subtypes except for moderate atypical depression.

MDD was characterized into four subtypes based on depressive symptoms and severity. Different stressor profiles were linked with various MDD subtypes. More specific interventions and clinical management are called to provide precision treatment for MDD patients with unique stressor profiles and MDD subtypes.

Major depressive disorder (MDD) is a leading cause of disability and premature mortality. This study compared the overall survival (OS) between patients with MDD and non-MDD controls stratified by gender, age, and comorbidities.

This nationwide population-based cohort study utilized longitudinal patient data (01/01/2010 – 12/31/2020) from the Hungarian National Health Insurance Fund database, which contains healthcare service data for the Hungarian population. Patients with MDD were selected and matched 1:1 to those without MDD using exact matching. The rates of conversion from MDD to bipolar disorder (BD) or schizophrenia were also investigated.

Overall, 471,773 patients were included in each of the matched MDD and non-MDD groups. Patients with MDD had significantly worse OS than non-MDD controls (hazard ratio [HR] = 1.50; 95% CI: 1.48−1.51; males HR = 1.69, 95% CI: 1.66–1.72; females HR = 1.40, 95% CI: 1.38–1.42). The estimated life expectancy of patients with MDD was 7.8 and 6.0 years less than that of controls aged 20 and 45 years, respectively. Adjusted analyses based on the presence of baseline comorbidities also showed that patients with MDD had worse survival than non-MDD controls (adjusted HR = 1.29, 95% CI: 1.28–1.31). After 11 years of follow-up, the cumulative conversions from MDD to BD and schizophrenia were 6.8 and 3.4%, respectively. Converted patients had significantly worse OS than non-converted patients.

Compared with the non-MDD controls, a higher mortality rate in patients with MDD, especially in those with comorbidities and/or who have converted to BD or schizophrenia, suggests that early detection and personalized treatment of MDD may reduce the mortality in patients diagnosed with MDD.

Major depressive disorder (MDD) is one of the most prevalent medical conditions worldwide. Different factors were found to play a role in its etiology, including environmental ones (e.g., air pollution). The aim of this study was to evaluate the association between air pollution exposure and MDD severity.

Four hundred sixteen MDD subjects were recruited. Severity of MDD and functioning were evaluated through five rating scales: Montgomery–Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAMD), Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), and Sheehan Disability Scale (SDS). Daily mean estimates of particulate matter with diameter ≤10 (PM10) and 2.5 μm (PM2.5), nitrogen dioxide (NO2), and apparent temperature (AT) were estimated based on subjects’ residential addresses. Daily estimates of the 2 weeks preceding recruitment were averaged to obtain cumulative exposure. Multivariate linear and ordinal regression models were applied to assess the associations between air pollutants and MDD severity, overall and stratifying by hypersusceptibility and AT.

Two-thirds of subjects were women and one-third had a family history of depression. Most women had depression with symptoms of anxiety, while men had predominantly melancholic depression. NO2 exposure was associated with worsening of MDD severity (HAMD: β = 1.94, 95% confidence interval [CI], [0.41–3.47]; GAF: β = −1.93, 95% CI [−3.89 to 0.02]), especially when temperatures were low or among hypersusceptible subjects. PM exposure showed an association with MDD severity only in these subgroups.

Exposure to air pollution worsens MDD severity, with hypersusceptibility and lower temperatures being exacerbating factors.

Cardiometabolic diseases (CMDs) including heart disease, stroke, and type 2 diabetes have been individually linked to depression. However, their combined impact on depression risk is unclear. We aimed to examine the association between cardiometabolic multimorbidity and depression and explore the role of genetic background in this association.

Within the Swedish Twin Registry, 40,080 depression-free individuals (mean age 60 years) were followed for 18 years. Cardiometabolic multimorbidity was defined as having ≥2 CMDs. CMDs and depression were ascertained based on the National Patient Register. Cox regression was used to estimate the CMD-depression association in a classical cohort study design and a matched co-twin design involving 176 twin pairs. By comparing the associations between monozygotic and dizygotic co-twins, the contribution of genetic background was estimated.

At baseline, 4809 (12.0%) participants had one CMD and 969 (2.4%) had ≥2 CMDs. Over the follow-up period, 1361 participants developed depression. In the classical cohort design, the multi-adjusted hazard ratios (95% confidence interval [CIs]) of depression were 1.52 (1.31–1.76) for those with one CMD and 1.83 (1.29–2.58) for those with ≥2 CMDs. CMDs had a greater risk effect on depression if they developed in mid-life (<60 years) as opposed to late life (≥60 years). In matched co-twin analysis, the CMD-depression association was significant among dizygotic twins (HR = 1.63, 95% CI, 1.02–2.59) but not monozygotic twins (HR = 0.90, 95% CI, 0.32–2.51).

Cardiometabolic multimorbidity is associated with an elevated risk of depression. Genetic factors may contribute to the association between CMDs and depression.

Obesity-related cardiometabolic comorbidity is common in major depressive disorder (MDD). However, sex differences and MDD recurrence may modify the MDD-obesity-link.

Sex-specific associations of MDD recurrence (single [MDDS] or recurrent episodes [MDDR]) and obesity-related traits were analyzed in 4.100 adults (51.6% women) from a cross-sectional population-based cohort in Germany (SHIP-Trend-0). DSM-IV-based lifetime MDD diagnoses and MDD recurrence status were obtained through diagnostic interviews. Obesity-related outcomes included anthropometrics (weight, body mass index, waist- and hip-circumference, waist-to-hip ratio, waist-to-height ratio), bioelectrical impedance analysis of body fat mass and fat-free mass, and subcutaneous (SAT) and visceral adipose tissue (VAT) from abdominal magnetic resonance imaging. Sex-stratified linear regression models predicting obesity-related traits from MDD recurrence status were adjusted for age, education, and current depressive symptoms.

790 participants (19.3%) fulfilled lifetime MDD criteria (23.8% women vs. 14.5% men, p<0.001). In women, MDDS was inversely associated with anthropometric indicators of general and central obesity, while MDDR was positively associated with all obesity-related traits, except waist-to-hip ratio and fat-free mass. In women, MDDR versus MDDS was associated with higher levels of obesity across all outcomes except fat-free mass. In men, MDD was positively associated with SAT regardless of MDD recurrence. Additionally, lifetime MDD was positively associated with VAT in men. Results remained significant in sensitivity analyses after exclusion of participants with current use of antidepressants.

The MDD-obesity association is modified by MDD recurrence and sex independent of current depressive symptoms. Accounting for sex and MDD recurrence may identify individuals with MDD at increased cardiometabolic risk.

Whether material deprivation-related childhood socio-economic disadvantages (CSD) and care-related adverse childhood experiences (ACE) have different impacts on depressive symptoms in middle-aged and older people is unclear.

In the Guangzhou Biobank Cohort Study, CSD and ACE were assessed by 7 and 5 culturally sensitive questions, respectively, on 8,716 participants aged 50+. Depressive symptoms were measured by 15-item Geriatric Depression Scale (GDS). Multivariable linear regression, stratification analyses, and mediation analyses were done.

Higher CSD and ACE scores were associated with higher GDS score in dose-response manner (P for trend <0.001). Participants with one point increment in CSD and ACE had higher GDS score by 0.11 (95% confidence interval [CI], 0.09–0.14) and 0.41 (95% CI, 0.35–0.47), respectively. The association of CSD with GDS score was significant in women only (P for sex interaction <0.001; women: β (95% CI)=0.14 (0.11–0.17), men: 0.04 (−0.01 to 0.08)). The association between ACE and GDS score was stronger in participants with high social deprivation index (SDI) (P for interaction = 0.01; low SDI: β (95% CI)=0.36 (0.29–0.43), high SDI: 0.64 (0.48–0.80)). The proportion of association of CSD and ACE scores with GDS score mediated via education was 20.11% and 2.28%.

CSD and ACE were associated with late-life depressive symptoms with dose-response patterns, especially in women and those with low adulthood socio-economic status. Education was a major mediator for CSD but not ACE. Eliminating ACE should be a top priority.

Hyponatremia (hypoNa) is a potentially serious adverse event of treatment with antidepressants. Previous research suggests that risk of drug-induced hyponatremia differs between antidepressants.

This meta-analysis sought to determine the risk of antidepressant-induced hypoNa, stratified by different compounds and classes.

PubMed and Web of Science were searched for studies reporting on incidence or risk of hypoNa in adults using antidepressants (PROSPERO, CRD42021269801). We modelled random-effects meta-analyses to compute overall incidence and risk of any and clinically relevant hypoNa for each compound and class, and ran head-to-head comparisons based on hypoNa incidences. We conducted subgroup analyses for geriatric populations, study context and sodium cut-off value.

Thirty-nine studies (n = 8,459,033) revealed that exposure to antidepressants was associated with significantly increased odds of hypoNa (OR = 2.82 (1.79 – 4.45)). The highest event rates were found for SNRIs (7.17%), SSRIs (5.20%), and TCAs (2.26%); the lowest for mirtazapine (1.02%) and trazodone (0.89%). The highest odds ratios were found for MAOIs (4.12 (1.92 – 8.86)), SNRIs (3.16 (1.77 – 5.67)), and SSRIs (2.78 (1.57 – 4.91)); the lowest for mirtazapine (2.82 (1.87 – 4.21)) and TCAs (1.85 (1.28 – 2.69)). Compared to SSRIs, SNRIs were significantly more likely (OR = 1.27 (1.13 – 1.42), p < 0.001) and mirtazapine significantly less likely (OR = 0.61 (0.39 – 0.96), p = 0.032) associated with hypoNa.

Our meta-analysis demonstrated that, while no antidepressant can be considered completely risk-free, for hypoNa-prone patients mirtazapine should be considered the treatment of choice and SNRIs should be prescribed more cautiously than SSRIs and TCAs.

None Declared

Cognitive reserve (CR) has been linked to dementia, yet its influence on the risk of depression and related outcomes remains unknown. We aimed to examine the association of CR with depression and subsequent dementia or death, and to assess the extent to which CR is related to depression-free survival.

Within the UK Biobank, 436,232 participants free of depression and dementia were followed. A comprehensive CR indicator (low, moderate, and high) was created using latent class analysis based on information on education, occupation, mentally passive sedentary behavior, social connection, confiding with others, and leisure activities. Depression, dementia, and survival status were ascertained through self-reported medical history and/or linkages to medical records. Data were analyzed using multi-state Markov model and Laplace regression.

Over a median follow-up of 12.96 years, 16,560 individuals developed depression (including 617 with subsequent dementia) and 28,655 died. In multivariable multi-state models, compared with low CR, high CR was associated with lower risk of depression (hazard ratio 0.53 [95% confidence interval 0.51–0.56]) and lower risk of post-depression dementia (0.55 [0.34–0.88]) or death (0.69 [0.55–0.88]) in middle-aged adults (aged <60 years). In Laplace regression, the depression-free survival time was prolonged by 2.77 (2.58–2.96) years in participants with high compared to low CR.

High CR is associated with lower risks of depression and subsequent transitions to dementia and death, particularly in middle age. High CR may prolong depression-free survival. Our findings highlight the importance of enhancing CR in the prevention and prognosis of depression.

Depression is one of the most prevalent mental health conditions in the world. However, the heterogeneity of depression has presented obstacles for research concerning disease mechanisms, treatment indication, and personalization. The current study used network analysis to analyze and compare profiles of depressive symptoms present in community samples, considering the relationship between symptoms.

Cross-sectional measures of depression using the Patient Health Questionnaire – 9 items (PHQ-9) were collected from community samples using data from participants scoring above a clinical threshold of ≥10 points (N = 2,023; 73.9% female; mean age 49.87, SD = 17.40). Data analysis followed three steps. First, a profiling algorithm was implemented to identify all possible symptom profiles by dichotomizing each PHQ-9 item. Second, the most prevalent symptom profiles were identified in the sample. Third, network analysis for the most prevalent symptom profiles was carried out to identify the centrality and covariance of symptoms.

Of 382 theoretically possible depression profiles, only 167 were present in the sample. Furthermore, 55.6% of the symptom profiles present in the sample were represented by only eight profiles. Network analysis showed that the network and symptoms’ relationship varied across the profiles.

Findings indicate that the vast number of theoretical possible ways to meet the criteria for major depressive disorder (MDD) is significantly reduced in empirical samples and that the most common profiles of symptoms have different networks and connectivity patterns. Scientific and clinical consequences of these findings are discussed in the context of the limitations of this study.

Theories propose that judgment of and reactivity to inner experiences are mediators of the effect of mindfulness-based interventions on generalized anxiety disorder (GAD). However, no study has tested such theories using brief, mindfulness ecological momentary intervention (MEMI). We thus tested these theories using a 14-day MEMI versus self-monitoring app (SM) control for GAD.

Participants (N = 110) completed self-reports of trait mindfulness (Five Facet Mindfulness Questionnaire), GAD severity (GAD-Questionnaire-IV), and trait perseverative cognitions (Perseverative Cognitions Questionnaire) at prerandomization, posttreatment, and 1-month follow-up (1MFU). Counterfactual mediation analyses with temporal precedence were conducted.

Improvement in pre–post mindfulness domains (acceptance of emotions, describing feelings accurately, acting with awareness, judgment of inner experience, and reactivity to inner experience) predicted pre-1MFU reduction in GAD severity and pre-1MFU reduction in trait perseverative cognitions from MEMI but not SM. MEMI reduced pre–post reactivity to inner experiences (but not other mindfulness domains) significantly more than SM. Only reduced pre–post reactivity significantly mediated stronger efficacy of MEMI over SM on pre-1MFU reductions in GAD severity (indirect effect: β = −2.970 [−5.034, −0.904], p = .008; b path: β = −3.313 [−6.350, −0.276], p = .033; percentage mediated: 30.5%) and trait perseverative cognitions (indirect effect: β = −0.153 [−0.254, −0.044], p = .008; b path: β = −0.145 [−0.260, −0.030], p = .014; percentage mediated: 42.7%). Other trait mindfulness domains were non-significant mediators.

Reactivity to inner experience might be a mindfulness-based intervention change mechanism and should be targeted to optimize brief MEMIs for GAD.

Amygdala subregion-based network dysfunction has been determined to be centrally implicated in major depressive disorder (MDD). Little is known about whether ketamine modulates amygdala subarea-related networks. We aimed to investigate the relationships between changes in the resting-state functional connectivity (RSFC) of amygdala subregions and ketamine treatment and to identify important neuroimaging predictors of treatment outcomes.

Thirty-nine MDD patients received six doses of ketamine (0.5 mg/kg). Depressive symptoms were assessed, and magnetic resonance imaging (MRI) scans were performed before and after treatment. Forty-five healthy controls underwent one MRI scan. Seed-to-voxel RSFC analyses were performed on the amygdala subregions, including the centromedial amygdala (CMA), laterobasal amygdala (LBA), and superficial amygdala subregions.

Abnormal RSFC between the left LBA and the left precuneus in MDD patients is related to the therapeutic efficacy of ketamine. There were significant differences in changes in bilateral CMA RSFC with the left orbital part superior frontal gyrus and in changes in the left LBA with the right middle frontal gyrus between responders and nonresponders following ketamine treatment. Moreover, there was a difference in the RSFC of left LBA and the right superior temporal gyrus/middle temporal gyrus (STG/MTG) between responders and nonresponders at baseline, which could predict the antidepressant effect of ketamine on Day 13.

The mechanism by which ketamine improves depressive symptoms may be related to its regulation of RSFC in the amygdala subregion. The RSFC between the left LBA and right STG/MTG may predict the response to the antidepressant effect of ketamine.